Diseño, estudio teórico computacional y síntesis de dos análogos estructurales de anandamida, como posibles ligandos de receptores cannabinoides CB1

Anandamide or N-arachidonoyl-ethanolamide (AEA) is an endocannabinoid compound that is synthesised from phospholipids present in the membranes of different cells, in the brain and in the peripheral nervous system. It is involved in biological processes such as: memory, movement control, attenuation of pain sensation, reproduction, among others. In addition, due to their lipophilic nature, they can cross the blood-brain barrier and generate psychoactive effects including euphoria, drowsiness, motor incoordination, alterations in temporal and spatial perception, disorientation and confusion. In order to counteract these effects, analogue structures were designed with lower theoretical partition coefficients of AEA and with a possible binding capacity to the endocannabinoid receptor type 1 (CB1). In this research, 30 anandamide analogues were designed, retaining ethanolamide as the neuromodulatory pharmacophore and using different bioisosteric groups as substituents. Subsequently, the Administration, Digestion, Metabolism, Excretion, Metabolism and Toxicity (ADMET) properties of these compounds were predicted and a molecular docking study was performed, determining the ligand-protein interactions and the affinity energy with the CB1 receptor. From these results, two AEA analogue structures were selected: (S)-3-(4 hydroxy-3-(1-hydroxyhexyl)phenyl)-N-(2-hydroxyethyl)propanamide (-104.45 kcal/mol) and (S)-3-(4-hydroxy-3-(1-hydroxyethyl)phenyl)-N-(2-hydroxyethyl)propanamide ( 98.60kcal/mol). The synthesis was from the 3-(4-hydroxyphenyl)propanoic acid compound obtained in the Chemical Systems laboratory of the UPTC. The preparation of the two Anandamide analogues was carried out using a four-step methodology: Friedel-Crafts orthoacylation, reduction, esterification and amidation. The products were purified and characterised by FTIR, 1H NMR and 13C NMR spectroscopy and mass spectrometry.

• Autores: Rojas Bustamante, Lida Rosmary
• Fecha de publicación: 2023
• Institución: Universidad Pedagógica y Tecnológica de Colombia
• Repositorio: RiUPTC: Repositorio Institucional UPTC
• OAI Identifier: oai:repositorio.uptc.edu.co:001/18268
• Acceso en línea: https://repositorio.uptc.edu.co/handle/001/18268
• Palabra clave: Maestría en Química -- Tesis y disertaciones académicas; Propiedad química; Gestión de los recursos hídricos; Administración de la ciencia; Metabolismo; Bioquímica
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-sa/4.0/